Figure 1. Neuropeptide cell-cell signaling in the nervous and endocrine systems.

A. Neuropeptides in the nervous system as peptide neurotransmitters. Neuropeptides are utilized as neurotransmitters for cell-cell communication in the brain and in the peripheral sympathetic and parasympathetic nervous system. Neuropeptides are synthesized within secretory vesicles that are transported from the neuronal cell body to nerve terminals. During axonal transport of such secretory vesicles, pro-neuropeptide precursors (or prohormone) are packaged into newly synthesized secretory vesicles with proteases for precursor processing into mature neuropeptides. Activity-dependent regulation of secretion releases neuropeptides at nerve terminals for neurotransmission.

B. Neuropeptides in the endocrine systems as peptide hormones. Neuropeptides function as peptide hormones to mediate cell-cell communication among brain and endocrine systems for regulation of physiological functions. Brain neuropeptides and endocrine peptide hormones are co-regulated in feedback systems for fine tuning of physiological regulation. For example, the hypothalamo-neurophypophyseal system regulates the pituitary-adrenal axis by secretion of CRF from the hypothalamus region of the brain to induce secretion of the ACTH peptide hormone from the pituitary. Released ACTH targets the adrenal cortex for stimulation of glucocorticoid production. Resultant increases in plasma glucocorticoid participate in feedback inhibition of CRF and ACTH to maintain constant levels of glucocorticoid. Numerous peptide hormones regulate physiological functions in stimulatory and feedback system.